The proposed research will seek to 1) develop a general method to perform catalytic asymmetric Nazarov cyclization and 2) achieve the total synthesis of two natural products, merrilactone A and tetrapetalone A using Nazarov cyclization as the key step. These natural products are neurotrophic and inhibit lipoxygenases, respectively. Synthesis of these structurally interesting compounds will allow us to explore unique chemical transformations and improve our ability to study the bioactivity of these molecules. The research will contribute potentially enantioselective strategies for the synthesis of these and other natural products with biologically significant behavior, enabling chemists to prepare and study pharmacological agents for medical applications. As an example of potential impact of these chemical methods, one specific aim of this application describes the synthesis of the neurotrophic agent merrilactone A. The ability to synthesize a molecule of this complexity and unusual bioactivity could eventually provide medical researchers with tools to combat neurodegenerative diseases, and methods to synthesize other molecules that will impact diseases important to public health.